SX-517

SX-517 is a dual CXCR2/1 antagonist, containing boronic acid. SX-517 inhibits CXCL1-induced Ca2+ flux (IC50=38 nM), and antagonizes CXCL8-induced [(35)S]GTPγS binding (IC50=60 nM) and ERK1/2 phosphorylation. SX-517 has significant ability for inflammation suppression, in both humanized polymorphonuclear (PMN) cells and in murine model.

SX-517 (compound 7) (0.1 nM-0.1 mM; 60 min) potently inhibits [35S]GTPγS binding induced by 10 nM CXCL8 with an IC50 of 60 nM^[1].
SX-517 (10 μM; 60 min) has inhibitory effect on the cell surface expression of CXCR2 in HEK293 cells^[1].
SX-517 (10 μM; 0-30 min) blocks CXCR2-mediated phosphorylation of ERK1/2 in HEK293 cells^[1].

SX-517 (compound 7) (0.2 mg/kg; iv; single dose) significantly inhibits inflammation in an in vivo murine model^[1].

References:
[1]. 2-[5-(4-Fluorophenylcarbamoyl)pyridin-2-ylsulfanylmethyl]phenylboronic Acid (SX-517): Noncompetitive Boronic Acid Antagonist of CXCR1 and CXCR2. J Med Chem. 2014 Oct 23;57(20):8378-97.
[2]. Ti H, et al. Targeted Treatments for Chronic Obstructive Pulmonary Disease (COPD) Using Low-Molecular-Weight Drugs (LMWDs). J Med Chem. 2019 Jul 11;62(13):5944-5978.